We will investigate the development of the mesencephalon, diencephalon, basal ganglia, and areal subdivisions of the neocortex in the rat as a preliminary step to the study of the development of visual, auditory, and somatosensory systems. The time of origin of neurons (cytogenesis) will be studied with 3H-thymidine autoradiography (progressively delayed, comprehensive labelling of embryos). The mode of dispersion and settling of neurons (histogenesis) will be examined in normal and X-irradiated embryonic brains in combination with autoradiography (using cytogenetic temporal gradients as indicators of settling patterns). Three-dimensional, scale reconstructions will be made of the transforming ventricles, neuroepithelia and differentiating zones as a function of age, and correlated with isochronic maps of adult brains derived from autoradiography. Axonal sprouting and dendritic maturation (neurodifferentiation) will be investigated in Golgi-impregnated fetal and postnatal brains. The establishment of fiber connections will be examined with a fiber tracing technique that is being adapted for use in exteriorized embryos. Finally, synaptogenesis in selected brain regions will be investigated with electron microscopy. In previous descriptive and experimental studies of the pre- and postnatal ontogeny of the cerebellum we obtained evidence that the precise chronology in the origin, dispersion and settling of neurons in the cerebellum and precerebellar brain stem nuclei is of importance for the establishment of normal cerebellar circuitry. We anticipate that a comparable approach to the major afferent systems of the brain will similarly yield insights about the role of chronological factors in the establishment of the gross and fine circuitry of these systems.